This invention relates to an improved process for the recovery of camphorsulfonic acids and more particularly, to an improved process for the purification and concentration of aqueous solutions of soluble salts of 10-d-camphorsulfonic acid.
Resolutions of racemic bases are carried out by means of the use of optically active acids. For example, 10-d-camphorsulfonic acid is an extremely effective resolving agent but it is costly. It must, therefore, be recovered efficiently and in a purified form to make a process economical.
An example of the use of 10-d-camphorsulfonic acid as a resolving agent is the resolution of DL-phenylglycine to D-phenylglycine, a material of importance in making semisynthetic penicillins. During the process a relatively dilute aqueous solution of 10-d-camphorsulfonic acid, as its sodium salt, is recovered along with other undesirable inorganic salts. The resolving agent needs to be concentrated and at the same time the inorganic salts removed selectively.
A liquid ion exchange method for recovering a concentrated purified aqueous solution of 10-d-camphorsulfonic acid is disclosed in U.S. Pat. No. 3,221,046. However, in order to obtain reasonable recoveries utilizing the patentees process it is necessary to utilize a multistage counter-current operation (3-5 theoretical stages). Another problem in this process is the instability of the system due to large volume changes in phases from stage to stage.
Theoretically, the problem can be explained in terms of competition for the exchange sites in the liquid ion exchanger. For example, if the only other anion in the aqueous phase were chloride (for example, from hydrochloric acid used to regenerate the 10-d-camphorsulfonic acid as was the case in the process described in U.S. Pat. No. 3,221,046) an equilibrium condition exists: EQU LA-1.sup.. HCl + CSA.sup.- .revreaction. La-1.sup.. HCSA + Cl.sup.-
wherein LA-1 is a liquid secondary amine or mixture thereof, CSA.sup.- is the anion of 10-d-camphorsulfonic acid, HCSA is 10-d-camphorsulfonic acid, and where the free ions are in the aqueous phase and acids are bound to the secondary amine, LA-1, in the organic phase. Assuming that this is truly the form of the equilibrium, an average value for the equilibrium constant was found from our experiments as follows: ##EQU1## where the subscripts A and o mean aqueous and organic phases respectively. The total number of sites in the organic phase is determined by the amount of acid present in the system until all the sites (capacity) are exhausted. Using the quantities normally used during the process, one can calculate that a single stage recovery process with hydrochloric acid recovers only about 72% of the camphorsulfonic acid.
The present invention resides in the use of a polyprotic acid, such as sulfuric acid, rather than a monoprotic acid, such as hydrochloric acid, to maintain the pH of the ion exchange system at a pH of 3 - 6. The selectivity of the liquid ion exchange process for a monoprotic anion over the diprotic sulfate is surprising since the opposite affect usually occurs when solid ion exchangers are used.
The equilibrium is written: EQU (LA-1.sup.. H).sub.2 SO.sub.4 + 2CSA.sup.- .revreaction. 2LA-1.sup.. HCSA + SO.sub.4 =
assuming that this is truly the form of the equilibrium, an average value for the equilibrium constant was found from our experiments as follows: ##EQU2## which gives a 92 - 98% recovery of 10-d-camphorsulfonic acid in the form of its sodium salt for a single stage recovery process. In order to have sulfate as the only anion competing with the camphorsulfonate, sulfuric acid would be used to regenerate the camphorsulfonic acid for the resolution process as well as being used in the recovery process.
Mixed polyprotic acids could be used in this process still giving a high selectivity for and high yield of the camphorsulfonic acid salt.